Biomedical subjects
T Susini
Publications and source records attributed to T Susini.
Management of benign adnexal masses by vaginal route.
Until recently, surgical treatment of a benign adnexal mass implied a laparotomy. In recent years, the development of laparoscopic surgery, as well as ultrasound-guided aspiration techniques, have significantly modified the treatment options for these patients. These procedures have shown considerable advantages. They have reduced surgical trauma and have shortened the hospital stay. We present the results of our experience on the feasibility of a trans-vaginal surgical approach for the removal of benign adnexal masses. This technique, using traditional and cheap surgical instruments, allows the surgeon to excise benign adnexal masses, by entering the peritoneum through the posterior vaginal fornix and thus avoids the trauma of laparotomy. Fifty-four patients were operated on by this technique at our Department. The mean age was 39 years (range 21-66). In all cases, the operation was completed by the trans-vaginal approach. The median operative time was 30 minutes (range 20-45), and no blood transfusion was needed. The pathological diagnoses were as follows: functional ovarian cyst; 19, endometriotic cyst; 18, dermoid cyst; 11, parovarian cyst; 4 and peduncolated fibroid of the uterine fundus; 2 cases. The diameter of the adnexal masses ranged from 3 to 10 cm (median of 6 cm). In 30 cases, a conservative surgery was done (including 2 myomectomies), whereas in 24 cases, the adnexectomy was needed. Median post-operative stay in hospital was 4 days (range 1-14). This study shows the feasibility of trans-vaginal surgical approach for benign adnexal masses. The advantages and limitations of this technique, as well as of the traditional and laparoscopic surgery are considered and discussed. We believe that the transvaginal approach could be useful and cost-effective for the treatment of selected cases of adnexal masses.
Flow cytometric measurement of DNA content in human solid tumors: a comparison with cytogenetics.
The aims of this study were: (1) to test the accuracy of flow cytometery (FC) in the measurement of DNA content in human solid tumors, (2) to correlate the FC DNA-index (DI) with the chromosome modal number (CMN) provided by cytogenetic analysis (CG), and (3) to investigate the most frequent pitfalls in FC histograms classification. FC and CG analyses were performed in parallel on 113 samples of human solid tumors of different origin. FC provided an evaluable histogram in 110 out of 113 cases (97%), whereas a successful CG culture was obtained in 79 out of 113 samples (72%). In the 79 cases evaluable by both FC and CG, a concordant ploidy status was found in 66 cases (84%) (47 diploid and 19 aneuploid) (P < 0.001, chi-square test). In the 19 concordant aneuploid tumors a close correlation between the CMN and the DI was found (y = 0.019 x + 0.151; r = 0.860). Concerning the 13 discordant cases, 11 (85%) were classified as aneuploid by FC and as diploid by CG, while 2 cases (15%) were CG aneuploid (1 near-diploid and 1 tetraploid) and FC diploid. The current study suggests that FC is a reliable method for the measurement of tumor DNA content of the studied solid tumors. Special attention should be paid to the improvement of DNA histograms quality, in order to reduce the difficulties in the detection of near-diploid and near-tetraploid cell populations. Multiple sampling should be warranted whenever possible.
Epithelial ovarian tumors in the reproductive age group: age is not an independent prognostic factor.
BACKGROUND: While ovarian carcinoma is rare in the reproductive age group, these younger patients are known to fare better than the older patients. To determine whether age is an independent prognostic factor, as well as to investigate the clinicopathologic profile and survival rate of young women with ovarian carcinoma, a retrospective analysis in a series of patients aged 40 years or younger was performed. METHODS: We collected data on 74 patients with borderline or invasive ovarian carcinoma treated at the Department of Obstetrics and Gynecology at the University of Florence between 1969 and 1994. The median follow-up was 72 months (range, 11-288 months). To assess the clinicopathologic profile and survival differences according to age, the series was subdivided into "very young" (30 years or younger) and "young" (31-40 years) groups of 34 and 40 patients, respectively. Survival rates (Kaplan-Meier method) were compared by the log rank test. A multivariate analysis (Cox proportional hazards) was used to determine the independent effect of each variable on survival. RESULTS: The overall 5-year and 10-year survival rates were 58.2% and 46.1%, respectively. Several prognostic factors were found significant by univariate analysis, including stage (P < 0.001), grade (P < 0.001), residual disease (P < 0.001), histologic type (P < 0.05), and age (< or = 30 years vs. 31-40 years; P = 0.009). Five year survival rates for the patients age 30 years and younger and patients age 31-40 years were 71.3% and 47.1%, respectively. In the former group, low malignant potential tumors and well differentiated carcinomas were significantly more frequent (68.8% vs. 37.5%; P = 0.01). In the multivariate analysis, only stage (I vs. >I; P = 0.004), grade (0-1 vs. 2-3; P = 0.03) and residual disease (P = 0.02) were found to be significant independent prognostic factors, whereas age (< or = 30 years vs. 31-40 years) yielded no independent information (P = 0.36). CONCLUSIONS: Epithelial ovarian cancer patients age 30 years or younger have a more favorable prognosis because of a higher rate of early stage, low grade tumors. Patients aged 31-40 years also show a more favorable disease profile and clinical outcome, although to a lesser extent, than the average ovarian cancer population. Age does not emerge as an independent prognostic factor for ovarian carcinoma in women younger than 40 years.
Three classes of radical vaginal hysterectomy for treatment of endometrial and cervical cancer.
OBJECTIVES: The aims of this study were to (1) describe three types of extended vaginal hysterectomy with different degree of radicality, (2) to identify possible indications for each one of them, and (3) to encourage individualization of the treatment, with special reference to the reevaluation of the role of vaginal surgery in gynecologic oncology. STUDY DESIGN: The surgical-anatomic principles of radical vaginal surgery and the techniques of three increasingly extended vaginal hysterectomies are illustrated. Possible indications are pointed out on the basis of our personal experience from previously published retrospective studies. RESULTS: Class I extended vaginal hysterectomy allows the "en bloc" dissection of the uterus along with the upper third of vagina and both the adnexa. The parametria are not removed. This procedure has proved to be of value for treatment of stage I endometrial cancer. In the class II extended vaginal hysterectomy the distal tract of the anterior and posterior parametria are preserved, whereas the cardinal ligament is entirely removed. This operation has shown promising results for treatment of stage IB-IIA cervical cancer of small volume while reducing the incidence of bladder and rectal dysfunctions. The class III procedure includes the complete removal of the parametria (anterior, lateral, and posterior). This operation has been shown to provide a high rate of cure for stage IB-IIA cervical cancer. CONCLUSIONS: In view of the several advantages of vaginal surgery, this approach should be considered in the individualized treatment of selected cases of endometrial and cervical cancers. The three classes of radical vaginal hysterectomy allow tailoring the type of vaginal operation to the clinical and physical characteristics of the patients. The combined use of extraperitoneal or laparoscopic lymphadenectomy would considerably extend the indications for radical vaginal operations.
Vaginal hysterectomy versus abdominal hysterectomy for the treatment of stage I endometrial adenocarcinoma.
OBJECTIVE: The aims of the current study were to (1) determine the effectiveness of vaginal hysterectomy for the treatment of stage I endometrial cancer and (2) analyze which clinical pathologic parameters were independent predictors of clinical outcome. STUDY DESIGN: In a retrospective analysis, 5- and 10-year results of vaginal hysterectomy were compared with those of abdominal hysterectomy in 327 cases of stage I adenocarcinoma. No preoperative irradiation was given. Overall, 180 patients underwent vaginal hysterectomy, whereas 147 patients had abdominal hysterectomy (106 cases with lymphadenectomy). The log-rank test was used for evaluation of survival differences. RESULTS: The 5- and 10-year survival rates (Kaplan-Meier method) were, respectively, 90% and 87% in the vaginal hysterectomy group and 91% and 90% in the abdominal hysterectomy group (difference not significant). The grade of differentiation, depth of myometrial invasion, and age were significantly correlated with survival, whereas histologic type, mode of surgery, lymphadenectomy, and adjuvant radiotherapy were not. In a multivariate analysis (Cox proportional hazards), grade of differentiation and age were independent predictors of clinical outcome, whereas depth of myometrial invasion lost significance. CONCLUSIONS: Vaginal hysterectomy showed a high rate of cure in stage I endometrial cancer. Therefore it can be used as an alternative to the abdominal operation in obese and poor surgical risk patients and, possibly, in selected low-risk cases.
Expression of endothelin-1 gene and protein in human granulosa cells.
Previous studies in animal models indicated an autocrine/paracrine action of endothelin-1 (ET-1) in the ovary. We now report evidence on the presence of ET-1 in human ovary during reproductive life. Immunohistochemical and in situ hybridization studies demonstrated a positive signal into cytoplasm of granulosa cells (GC) of follicles at different growth stages. The concentration of ET-1-like immunoreactivity (ET-1-LI) was also measured by a specific RIA in human follicular fluid (FF). FF samples were obtained from women in an in vitro fertilization program undergoing gonadotropin stimulation (group A; n = 24) or no treatment (group B; n = 7). The mean (+/-SD) ET-1-LI FF level in group A (4.85 +/- 2.06 pg/mL) was significantly higher than that in group B (1.29 +/- 0.43 pg/mL; P < 0.01), whereas the corresponding mean plasma levels were not significantly different and were not correlated to respective FF values. Our results indicate for the first time the presence of ET-1 and its messenger ribonucleic acid in the GC of the human ovary. The higher ET-1-LI levels found in the FF from women undergoing gonadotropin treatment suggest a modulation by gonadotropins and/or ovarian steroids of ET-1 production by GC.
Sex steroid modulation of AT2 receptors in human myometrium.
In contrast to the abundant expression of the AT2 subtype of angiotensin II (AII) receptors during fetal development, AT2 receptor in adult life is expressed in few tissues. We now report studies on the presence and hormonal regulation of AT2 receptor in human pregnant and nonpregnant myometrium obtained from a large study population (n = 50). AT2 receptor subtypes have been characterized using self- and cross-competition curves among [125I]CGP42112A (a selective AT2 ligand), [125I](Sar1,Ile8)AII (a unselective antagonist), the corresponding unlabeled ligands, and several peptidic and nonpeptidic analogs with different affinities for the AT1 and AT2 receptor subtypes. We found that the human nonpregnant uterus expresses almost exclusively the AT2 subtype, and that [125I]CGP42112A is a selective probe to study human AT2 receptor. By using [125I]CGP42112A, we demonstrated that the density of AT2 receptor in human myometrium is dramatically affected by the hormonal milieu. Indeed, in the estrogen-dominant uterus of normal cycling women in the proliferative phase and that of perimenopausal women with anovulatory cycles, the density of binding sites was very high [1565 +/- 246 fmol/mg protein (n = 11) and 2176 +/- 429 (n = 7), respectively]. The concomitant presence of progestogens blunted the estrogen effect [term pregnancy, 61 +/- 12 fmol/mg protein (n = 5); secretive phase of the cycle, 453 +/- 154 (n = 10); combined oral contraceptive, 243 +/- 74 fmol/mg protein (n = 6)]. Very low concentrations of binding sites are also present in the sex steroid-deprived uterus of postmenopausal women (100 +/- 12 fmol/mg protein; n = 8) and the uterus of fertile women chronically treated with GnRH agonists (199 +/- 100 fmol/mg protein; n = 3). Hence, these data confirm the presence of AT2 receptors in human uterus and indicate their regulation by sex steroids.
Ureteral obstruction due to retroperitoneal endometriosis: a conservative approach including surgery and GnRH analogs.
Ureteral obstruction due to endometriosis is an infrequent condition which can be asymptomatic for a long time. Irreversible loss of renal function may result in cases with delayed diagnosis. Our report concerns a case of unilateral hydronephrosis and hypertension due to retroperitoneal endometriosis occurring in a 24-year-old woman. The management of patients bearing obstructive uropathy caused by endometriosis is discussed. In the present case, a conservative operation followed by medical treatment, including GnRH analogs, was used to preserve reproductive capacity.
Pregnancy-associated ectopic decidua.
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Hormonal and local regulation of uterine activity during parturition: Part I--The oxytocin system.
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Hormonal and local regulation of uterine activity during parturition: Part II--The prostaglandin and adrenergic systems.
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Platelet-activating factor in human endometrium.
Platelet-activating factor (PAF) is a phospholipid actively produced by human endometrium and deeply involved in the processes of ovoimplantation and labor. We recently found that PAF represents a new autocrine growth factor for a human adenocarcinoma cell line, HEC-1A. Indeed, biologically active PAF is synthesized by HEC-1A cells, under progesterone control. In HEC-1A cells, PAF regulates intracellular calcium concentration ([Ca2+]), DNA synthesis and expression of early oncogenes. All these effects are blocked by the receptor antagonist L659,989. However, while nanomolar concentrations of PAF mobilize [Ca2+], only micromolar concentrations affect cell growth, suggesting heterogeneity of PAF receptors or signaling. Two distinct populations of PAF receptors are present in HEC-1A cells, which bind PAF in nanomolar and micromolar concentrations, respectively. Since HEC-1A cells are producing elevated concentrations of PAF and micromolar concentrations of the PAF antagonist L659,989 inhibit cell proliferation, an autocrine role for PAF is suggested in HEC-1A cells.
Prognostic value of flow cytometric deoxyribonucleic acid index in endometrial carcinoma: comparison with other clinical-pathologic parameters.
OBJECTIVE: The aims of the current study were to verify the impact of flow cytometric deoxyribonucleic acid index on clinical outcome in endometrial carcinoma and to assess whether its value is independent from the other clinical-pathologic features. STUDY DESIGN: In a prospective series 74 cases of endometrial carcinoma with surgery performed at our institution were studied. Flow cytometry was performed on fresh tumor samples. The median follow-up period was 31 months (range 8 to 52). Disease-free survival and actuarial survival were the end points of the study. RESULTS: Among the 74 patients (53 with diploid and 21 with aneuploid tumors) there were 14 recurrences and 10 deaths caused by the disease. The recurrence rate was 7.5% for the diploid and 47.6% for the aneuploid tumors (p < 0.001). Mortality was 3.8% for diploid and 38% for aneuploid cases (p < 0.001). Disease-free survival was 89.1% in the former group and 36.3% in the latter. Actuarial survival (Kaplan-Meier method) was 94.7% and 49.5%, respectively. Deoxyribonucleic acid index, stage (International Federation of Gynecology and Obstetrics), and grade of differentiation were significantly correlated with survival, whereas age, depth of myometrial invasion, and histologic type were not. In a multivariate analysis (Cox proportional hazards) deoxyribonucleic acid index was the strongest independent predictor of clinical outcome, followed by International Federation of Gynecology and Obstetrics stage, whereas grade of differentiation yielded no independent prognostic information. CONCLUSIONS: The flow cytometric deoxyribonucleic acid index is an important independent prognosticator, and its determination should be included in the standard management of endometrial cancer.
Schauta-Amreich vaginal hysterectomy and Wertheim-Meigs abdominal hysterectomy in the treatment of cervical cancer: a retrospective analysis.
OBJECTIVE: The aim of the current study was to determine the effectiveness of Schauta's vaginal hysterectomy in the treatment of stage IB or IIA cervical carcinoma. STUDY DESIGN: In a retrospective analysis the results of Schauta's operation have been compared with those of Meigs' operation in 793 consecutive cases of stage IB or IIA cervical carcinoma. In 201 of them adjuvant radiotherapy was given. A total of 356 patients with stage IB and 76 with stage IIA underwent Schauta's operation, whereas 288 and 64 patients with stage IB and IIA, respectively, were operated on with Meigs' procedure. For statistical analysis the Mantel-Haenszel test was used. RESULTS: In stage IB the 5-year survival (Kaplan and Meier method) was 81% in the Schauta group and 75% in the Meigs group (p < 0.05). The results for stage IIA were 68% and 64%, respectively (difference not significant). In a separate analysis for stage IB and treatment by surgery alone, 5-year survival rates for the 283 in the Schauta group and the 175 in the Meigs group were 83% and 78%, respectively (difference not significant). CONCLUSION: Schauta's vaginal hysterectomy showed a high rate of cure for stage IB or IIA cervical cancer. Therefore we conclude that it can be used as an alternative to the Meigs operation in the presence of obesity or elevated surgical risk.
GnRH analogs in gynecological oncology: a review.
Chronic GnRH analogs (GnRH-A) administration has proven to be effective for the control of some hormone-dependent tumors. GnRH-A are now in the standard treatment of prostatic cancer. In the present paper experimental and clinical data on the use of GnRH-A in gynecologic oncology are reviewed in order to identify a possible role in the therapy of breast, endometrial and ovarian cancer. Besides the indirect hormonal effect of GnRH-A, mediated by the suppression of gonadal steroidogenesis, in vitro evidence suggests a direct anti-proliferative action involving autocrine-paracrine regulation of cellular function. In advanced or recurrent breast cancer objective responses were observed in 157 out of 378 premenopausal patients (41%) and in 18 out of 166 postmenopausal women (10%). In ovarian cancer complete and partial responses were observed in 14 out of 121 (11%). At present, data on advanced endometrial carcinoma are limited: only 18 treated patients are reported, of whom 7 responded (38.8%). However, in general, most of the responses observed were transient. Thus, so far, the use of GnRH-A in gynecologic oncology has to be considered for palliation, after the failure of other better understood treatment modalities. The possible use of GnRH-A as an adjuvant is still under investigation.
Gastric motor responses elicited by vagal stimulation and purine compounds in the atropine-treated rabbit.
1. The effects of vagal inhibitory stimulation and of purine compounds were studied in the rabbit stomach. 2. Gastric motility was assessed by the balloon method. Vagal nerves were electrically stimulated at the neck. Purine compounds were injected intra-arterially. 3. In the atropine-treated rabbit, vagal stimulation caused relaxant motor responses followed by a rebound contraction. 4. Among the purine compounds, only ADP and ATP caused relaxant motor responses similar to the effects of vagal inhibitory stimulation. However, the relaxation produced by ATP was more powerful than that due to ADP, especially at lower infusion rates. 5. Vagal inhibitory responses were recorded during and after infusion of ATP. When relaxation by ATP was fully developed, vagal inhibitory stimulation was ineffective. At the highest infusion rates of ATP, a depression of the vagal inhibitory motility was also observed after cessation of the infusion. 6. Relaxant responses to ATP and vagal inhibitory stimulation were not influenced by theophylline, scarcely affected by alpha,beta-methylene ATP, but were reduced or blocked by reactive blue 2. 7. The results are consistent with ATP being an inhibitory neurotransmitter in the stomach of the rabbit.